Important events in the pathogenesis of atherosclerosis are associated with the loss of the integrity of the vascular endothelium. Endothelium is unique in that its function is dependent on the continuity of a monolayer of highly differentiated cells growing on a collagenous surface which is continuously exposed to flow and pulsation. We propose a combined microcinematographic, ultrastructural and limited biochemical study of isolated vascular endothelial cells exposed in vitro to controlled flow and stretch conditions, to define the processes of cell adhesion, migration, replication and connective tissue dynamics involved in the maintenance of the integrity of endothelium. We extended these studies to include capillary endothelium, which recently became available in our laboratories. The motility of these cells is important in tumor angiogenesis, inflammation, wound healing and in the morphogenesis of the entire cardiovascular system in the embryo. Aortic and capillary endothelial cells are grown on collagen incorporated into hydroxmethylmet acrylate/methylmetacrylate copolymers ("hydrogels"). We will evaluate the ability of various collagens to support endothelial cell adhesion, migration, replication and tube formation under the influence of flowing media and pulsating substrates. Direct microcinematographic observation and quantitative assessment of cell adhesion and migration will be correlated with transmission- and scanning electron microscopy, incorporation of 3H-thymidine into DNA, and biochemical analysis of some steps in collagen metabolism. The goal of the study is the elucidation of the principal dynamic mechanisms involved in the maintenance of the functional and morphological integrity of endothelium.